Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Jul;91(3):531–537. doi: 10.1111/j.1476-5381.1987.tb11246.x

A comparison of excitatory amino acid antagonists acting at primary afferent C fibres and motoneurones of the isolated spinal cord of the rat.

R H Evans, S J Evans, P C Pook, D C Sunter
PMCID: PMC1853540  PMID: 3038242

Abstract

The potency of 7 excitatory amino acid antagonists had been measured at kainate receptors on primary afferent C fibres using isolated dorsal roots from immature rats. Two of the compounds were tested as antagonists of excitant amino acids at motoneurones using isolated hemisected spinal cord preparations. Mean dose-ratios for antagonism of kainate at C fibres, produced by 1 mM antagonist in at least four preparations, ranged from 2.1 +/- 0.5 (mean +/- s.e.mean) with 2-amino-5-phosphonopentanoate (AP5) to 17.6 +/- 2.4 with 1-(p-bromobenzoyl)-piperazine-2, 3-dicarboxylate (BBpzD). The rank order of potency of antagonists at C fibres was similar to that obtained previously for antagonism of kainate at motoneurones. The potency of kynurenate as an antagonist of kainate at C fibres (apparent Kd 70 +/- 4.3 microM (mean +/- s.e.mean), n = 12) was significantly different (P less than 0.005, Wilcoxon rank sum) from its potency at motoneurones (apparent Kd 164 +/- 14 microM, n = 13). Kynurenate also was significantly (P less than 0.025 Wilcoxon rank sum) more potent at antagonizing kainate- than quisqualate (apparent Kd 258 +/- 28 microM, n = 12)-induced depolarization of motoneurones. Kynurenate and BBpzD (0.25, 1.0 and 4.0 mM) were compared as antagonists of N-methyl-D-aspartate (NMDA) at motoneurones and the slope of the Gaddum-Schild plot for kynurenate was markedly greater than 1 (2.01 +/- 0.22, 95% confidence limits). A greater than additive antagonism of NMDA-induced depolarizations was produced by combinations of kynurenate with, either AP5, or magnesium ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
531

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agrawal S. G., Evans R. H. The primary afferent depolarizing action of kainate in the rat. Br J Pharmacol. 1986 Feb;87(2):345–355. doi: 10.1111/j.1476-5381.1986.tb10823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anis N. A., Berry S. C., Burton N. R., Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983 Jun;79(2):565–575. doi: 10.1111/j.1476-5381.1983.tb11031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berry S. C., Dawkins S. L., Lodge D. Comparison of sigma- and kappa-opiate receptor ligands as excitatory amino acid antagonists. Br J Pharmacol. 1984 Sep;83(1):179–185. doi: 10.1111/j.1476-5381.1984.tb10133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies J., Evans R. H., Francis A. A., Jones A. W., Watkins J. C. Antagonism of excitatory amino acid-induced and synaptic excitation of spinal neurones by cis-2,3-piperidine dicarboxylate. J Neurochem. 1981 Mar;36(3):1305–1307. doi: 10.1111/j.1471-4159.1981.tb01736.x. [DOI] [PubMed] [Google Scholar]
  5. Davies J., Jones A. W., Sheardown M. J., Smith D. A., Watkins J. C. Phosphono dipeptides and piperazine derivatives as antagonists of amino acid-induced and synaptic excitation in mammalian and amphibian spinal cord. Neurosci Lett. 1984 Nov 23;52(1-2):79–84. doi: 10.1016/0304-3940(84)90354-9. [DOI] [PubMed] [Google Scholar]
  6. Evans R. H., Francis A. A., Jones A. W., Smith D. A., Watkins J. C. The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations. Br J Pharmacol. 1982 Jan;75(1):65–75. doi: 10.1111/j.1476-5381.1982.tb08758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans R. H., Watkins J. C. Specific antagonism of excitant amino acids in the isolated spinal cord of the neonatal rat. Eur J Pharmacol. 1978 Jul 15;50(2):123–129. doi: 10.1016/0014-2999(78)90007-9. [DOI] [PubMed] [Google Scholar]
  8. Ganong A. H., Lanthorn T. H., Cotman C. W. Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res. 1983 Aug 22;273(1):170–174. doi: 10.1016/0006-8993(83)91108-3. [DOI] [PubMed] [Google Scholar]
  9. Harrison N. L., Simmonds M. A. Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381–391. doi: 10.1111/j.1476-5381.1985.tb12922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jones A. W., Smith D. A., Watkins J. C. Structure-activity relations of dipeptide antagonists of excitatory amino acids. Neuroscience. 1984 Oct;13(2):573–581. doi: 10.1016/0306-4522(84)90250-1. [DOI] [PubMed] [Google Scholar]
  11. Martin D., Lodge D. Ketamine acts as a non-competitive N-methyl-D-aspartate antagonist on frog spinal cord in vitro. Neuropharmacology. 1985 Oct;24(10):999–1003. doi: 10.1016/0028-3908(85)90128-5. [DOI] [PubMed] [Google Scholar]
  12. Olverman H. J., Jones A. W., Watkins J. C. L-glutamate has higher affinity than other amino acids for [3H]-D-AP5 binding sites in rat brain membranes. Nature. 1984 Feb 2;307(5950):460–462. doi: 10.1038/307460a0. [DOI] [PubMed] [Google Scholar]
  13. Perkins M. N., Stone T. W. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982 Sep 9;247(1):184–187. doi: 10.1016/0006-8993(82)91048-4. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES